Background:Percutaneous closure has replaced surgery for the majority of cases of secundum atrial septal defect (ASD). However, technological advances have made contemporary minimally invasive ...cardiac surgery (MICS) less invasive than conventional surgery. The aim of this study was to compare clinical outcomes of percutaneous closure of secundum ASD with those of contemporary MICS.Methods and Results:We conducted a single-center retrospective study of 354 patients with ASD treated either with the Amplatzer Septal Occluder (134 patients) or MICS (220 patients) between 2000 and 2013. Success rates and the incidence of complications were compared. The success rates were 98% for percutaneous closure and 100% for MICS. There were no deaths in either group. Major complications occurred in 2 patients (1.5%) who underwent percutaneous closure and in 8 patients (3.6%) treated with MICS (P=0.16). Minor complications occurred in 15 patients (11.2%) who underwent percutaneous closure and in 46 patients (20.9%) treated with MICS (P=0.02). On multivariate analysis, MICS (odds ratio OR: 2.91, 95% confidence interval CI: 1.46–5.81; P=0.002) and age >70 years (OR: 3.50, 95% CI: 1.40–8.75; P=0.008) were independent predictors of complications.Conclusions:Percutaneous closure and MICS had high success rates without deaths. For ASD patients with a suitable anatomy, percutaneous closure can be considered as the first therapeutic option.
Colorectal and gastric cancers are a leading cause of cancer deaths in developed countries. Precise estimation of prognosis is important with regard to clinical decision making for individuals with ...such cancers. We here comprehensively compiled a complete atlas of prognostic genes based on an integrated meta-analysis of one of the largest assembled colorectal cancer cohorts. A simple yet robust machine learning approach was then applied to establish a universal molecular prognostic score (mPS_colon) that relies on the expression status of only 16 genes and which was validated with independent data sets. This score was found to be an independent prognostic indicator in multivariate models including cancer stage, to be valid independent of tumor characteristics or patient ethnicity, and to be also applicable to gastric cancer. We conclude that mPS_colon is a universal prognostic classifier for patients with gastrointestinal cancers and that it should prove informative for optimization of personalized therapy for such patients.
Quantification of skill level in surgical training is necessary for effective skill development. In this study, we report the development of a smartphone application that automatically and ...objectively evaluates training in stitching goldfish scoop poi, a fragile material currently used for practice by young surgeons in Japan.
The application, named “e-Suture,” enables the automatic evaluation of surgical technique quality by evaluating the gap between the mark printed on the poi and the insertion/extraction point of the needle (Accuracy), analyzing suture placement (Deflection), detecting tears in the poi material/tissue (Tears), and the time taken to perform the exercise (Time). The algorithm for scoring used a sigmoid function, and the coefficients were adjusted so that the scores of a sample of 20 cases ranged between 20 and 100 points.
The e-Suture prototype was completed. The e-Suture-derived ranking for 20 poi after training was significantly correlated with the mean of the rankings evaluated by 9 experts (correlation coefficient: 0.728; p = 0.000). We also tested which items the experts rated as the most important. The overall ratings obtained from the experts correlated with the e-Suture accuracy scoring results with a correlation coefficient of 0.836 (p = 0.000) for Accuracy, 0.31 (p = 0.173) for Deflection, and 0.518 (p = 0.019) for Tear.
The e-Suture application can easily and accurately quantify and evaluate the suturing skills of novie surgeons. Further studies should improve the accuracy of data to be analyzed by collecting more surgical data and applying it to other surgical techniques.
Abstract
Saphenous veins (SVs) are frequently employed as bypass grafts. The SV graft failure is predominantly seen at the valve site. Avoiding valves during vein harvest would help reduce graft ...failure. We endeavored to detect SV valves, tributaries, and vessel size employing upright computed tomography (CT) for the raw cadaver venous samples and in healthy volunteers. Five cadaver legs were scanned. Anatomical analysis showed 3.0 (IQR: 2.0–3.0) valves and 13.50 (IQR: 10.00–16.25) tributaries. The upright CT completely detected, compared to 2.0 (IQR: 1.5–2.5,
p
= 0.06) valves and 9.5 (IQR: 7.5–13.0,
p
= 0.13) tributaries by supine CT. From a total of 190 volunteers, 138 (men:75, women:63) were included. The number of valves from the SF junction to 35 cm were significantly higher in upright CT than in supine CT bilaterally upright vs. supine, Right: 4 (IQR: 3–5) vs. 2 (IQR:1–2),
p
< 0.0001, Left: 4 (IQR: 3–5) vs. 2 (IQR: 1–2),
p
< 0.0001. The number of tributaries and vessel areas per leg were also higher for upright compared with supine CT. Upright CT enables non-invasive detection of SV valves, tributaries, and vessel size. Although not tested here, it is expected that upright CT may potentially improve graft assessment for bypass surgery.
Abstract
Although ribosome-profiling and translation initiation sequencing (TI-seq) analyses have identified many noncanonical initiation codons, the precise detection of translation initiation sites ...(TISs) remains a challenge, mainly because of experimental artifacts of such analyses. Here, we describe a new method, TISCA (TIS detection by translation Complex Analysis), for the accurate identification of TISs. TISCA proved to be more reliable for TIS detection compared with existing tools, and it identified a substantial number of near-cognate codons in Kozak-like sequence contexts. Analysis of proteomics data revealed the presence of methionine at the NH2-terminus of most proteins derived from near-cognate initiation codons. Although eukaryotic initiation factor 2 (eIF2), eIF2A and eIF2D have previously been shown to contribute to translation initiation at near-cognate codons, we found that most noncanonical initiation events are most probably dependent on eIF2, consistent with the initial amino acid being methionine. Comprehensive identification of TISs by TISCA should facilitate characterization of the mechanism of noncanonical initiation.
Graphical Abstract
Graphical Abstract
TISCA reliably identifies translation initiation sites (TISs) and provides insight into the mechanism of translation initiation at near-cognate codons. TISCA efficiently reduces the background noise in GTI-seq analysis. The absence and nonrelease of eIF3-seq footprints are mostly eliminated as noise. Red and blue circles show the 5′ end of a GTI-seq peak and an eIF3 release point, respectively. TIS candidates are located at +11 to +13 nt from the GTI-seq peak and at −22 to −26 nt from the eIF3 release point (top). TISCA identifies a substantial number of near-cognate initiation codons, most of which are translated in a manner dependent on eIF2–Met-tRNAi (bottom).
Fbxw7 is an F-box protein that contributes to regulation of cell proliferation and cell fate determination as well as to tumor suppression in various tissues. In this study, we generated mice with ...mammary gland-specific ablation of Fbxw7 (
mice) and found that most neonates born to mutant dams die soon after birth as a result of defective maternal lactation. The mammary gland of mutant dams was markedly atrophic and manifested both excessive cell proliferation and apoptosis in association with the accumulation of Notch1 and p63. Despite the hypoplastic nature of the mutant mammary gland,
/
mice spontaneously developed mammary tumors that resembled basal-like carcinoma with marked intratumoral heterogeneity. Additional inactivation of
in
/
mice further promoted onset and development of mammary tumors, suggesting that spontaneous mutation of
may facilitate transition of hypoplastic mammary lesions to aggressive cancer in mice lacking Fbxw7. RNA-sequencing analysis of epithelial- and mesenchymal-like cell lines from a
/
mouse tumor revealed an increased mutation rate and structural alterations in the tumor and differential expression of upstream transcription factors including known targets of Fbxw7. Together, our results implicate Fbxw7 in the regulation of cell differentiation and in tumor suppression in the mammary gland. Loss of Fbxw7 increases mutation rate and chromosome instability, activates signaling pathways governed by transcription factors regulated by Fbxw7, and triggers the development of mammary tumors with prominent heterogeneity. SIGNIFICANCE: Mammary gland-specific ablation of Fbxw7 in mice results in defective gland development and spontaneous mammary tumor formation reminiscent of human basal-like carcinoma with intratumoral heterogeneity. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/24/5515/F1.large.jpg.
Estrogen receptor α (ERα) is a transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast cancers. The molecular mechanisms underlying the ...up-regulation of ERα activity, however, remain poorly understood. We identified FK506-binding protein 52 (FKBP52) as a factor associated with poor prognosis of individuals with ERα-positive breast cancer. We found that FKBP52 interacts with breast cancer susceptibility gene 1 and stabilizes ERα, and is essential for breast cancer cell proliferation. FKBP52 depletion resulted in decreased ERα expression and proliferation in breast cancer cell lines, including MCF7-derived fulvestrant resistance (MFR) cells, suggesting that inhibiting FKBP52 may provide a therapeutic effect for endocrine therapy–resistant breast cancer. In contrast, FKBP51, a closely related molecule to FKBP52, reduced the stability of ERα. Consistent with these findings, FKBP51 was more abundantly expressed in normal tissues than in cancer cells, suggesting that these FKBPs may function in the opposite direction. Collectively, our study shows that FKBP52 and FKBP51 regulate ERα stability in a reciprocal manner and reveals a regulatory mechanism by which the expression of ERα is controlled.
Adverse climate change attributed to elevated atmospheric carbon dioxide concentration (CO₂) and increased temperature components of global warming has been a central issue affecting economic and ...social development. Climate change, particularly global warming, imposes a severe impact on the terrestrial ecosystem. Elevated CO₂, drought, and high temperature have been extensively documented individually; however, relatively little is known about how plants respond to the interaction of these factors. To summarize current knowledge on the response of plants to global change factors, we focus on the interactive effects of CO₂ enrichment, warming, and drought on plant growth, carbon allocation, and photosynthesis. Stimulation due to elevated CO₂ might be suppressed under other negative climatic/environmental stresses such as drought, high temperature, and their combination. However, elevated CO₂ could alleviate deleterious effects of moderate drought via reducing stomatal conductance, altering leaf surface, and regulating gene expression. High CO₂ levels and rising temperatures may result in opposite responses in plant water use efficiency. Stimulation of plant growth due to elevated CO₂ for C₃ species occurs regardless of water conditions, but only under a water deficit for C₄ species. The positive effect of elevated CO₂ on C₄ species is derived mainly from the improved water status. Plant adaptive or maladaptive responses to multivariate environments are interactive; thus, researchers need to explore the ecological underpinnings involved in such responses to the multiple factors involved in climate change.
Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently ...been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H
O
) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H
O
by high glucose, and H
O
reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E-fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.
Analyzing the spatial patterns and associations among tree species may help to elucidate the importance of the ecological processes behind population formation and the mechanisms of species ...coexistence. To explore this mechanism, we mapped and studied eight dominant tree species in Korean pine broad-leaved mixed forests in a temperate forest region in Jilin Province, Northeast China. The spatial distribution patterns and spatial associations of the eight dominant tree species at different life history stages and spatial scales were analyzed using the second-order spatial point pattern method based on pair correlation functions. The results indicated the following: (1) The diameter class structure of all individuals in the plots showed an obvious “L” shape, indicating that the community was well regenerated and belonged to a growing stand. (2) The distribution of trees was affected by scale, size, and habitat heterogeneity. The degree of aggregation decreased as the diameter class increased. (3) Out of the 56 pairs of individuals, a small number showed a significant correlation, while most were negatively correlated. It is concluded that seed dispersal limitations, competitive ability, and topography and light requirements may influence the spatial distribution and association of species to maintain species coexistence and diversity in Korean pine broad-leaved mixed forests. The results can provide insights into the ecological processes of population assembly, the mechanisms of species coexistence, and the relationship between forest management and restoration.
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